Directed differentiation of human embryonic stem cells toward chondrocytes

被引：215

作者：

Oldershaw, Rachel A. ^{[1
]}

Baxter, Melissa A. ^{[1
]}

Lowe, Emma T. ^{[1
,2
]}

Bates, Nicola ^{[1
]}

Grady, Lisa M. ^{[1
]}

Soncin, Francesca ^{[3
]}

Brison, Daniel R. ^{[1
,4
]}

Hardingham, Timothy E. ^{[1
,2
]}

Kimber, Susan J. ^{[1
]}

机构：

[1] Univ Manchester, N W Embryon Stem Cell Ctr, Fac Life Sci, Core Technol Facil, Manchester, Lancs, England

[2] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Fac Life Sci, Manchester, Lancs, England

[3] Univ Manchester, Fac Med & Human Sci, Core Technol Facil, Manchester, Lancs, England

[4] Cent Manchester Univ Hosp NHS Fdn Trust, Dept Reprod Med, St Marys Hosp Women & Children, Manchester, Lancs, England

来源：

NATURE BIOTECHNOLOGY | 2010年 / 28卷 / 11期

基金：

英国医学研究理事会;

关键词：

CHONDROGENIC DIFFERENTIATION; DEFINITIVE ENDODERM; IN-VITRO; MESSENGER-RNA; STROMAL CELLS; MESODERM; EXPRESSION; INDUCTION; SOX9; SPECIFICATION;

D O I：

10.1038/nbt.1683

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We report a chemically defined, efficient, scalable and reproducible protocol for differentiation of human embryonic stem cells (hESCs) toward chondrocytes. HESCs are directed through intermediate developmental stages using substrates of known matrix proteins and chemically defined media supplemented with exogenous growth factors. Gene expression analysis suggests that the hESCs progress through primitive streak or mesendoderm to mesoderm, before differentiating into a chondrocytic culture comprising cell aggregates. At this final stage, 74% (HUES1 cells) and up to 95-97% (HUES7 and HUES8 cells) express the chondrogenic transcription factor SOX9. The cell aggregates also express cell surface CD44 and aggrecan and deposit a sulfated glycosaminoglycan and cartilage-specific collagen II matrix, but show very low or no expression of genes and proteins associated with nontarget cell types. Our protocol should facilitate studies of chondrocyte differentiation and of cell replacement therapies for cartilage repair.

引用

页码：1221 / U80

页数：10

共 60 条

[1] The transcrintion factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6 [J].